基於網絡藥理學探討靈芝治療特應性皮炎的分子作用機制及有效成分

目的：應用網絡藥理學方法，研究靈芝治療特應性皮炎（濕疹）的分子機制及有效成分。方法：用TCMSP 數據庫篩選靈芝成分；用Swiss Target Prediction網站預測每個成分的作用靶點；在OMIM、GeneCards和TTD 疾病基因數據庫中收集濕疹有關的基因；確定藥物-疾病共同靶點後，用STRING數據庫建立「蛋白質互作網絡」 （PPI網絡），用Cytoscape 3.8.2軟件及R軟件分析網絡拼作圖。結果：篩選出61種靈芝活性成分。從成分的靶點和濕疹有關的基因中得到101個共同的基因，作為靈芝治療濕疹的潛在靶點。通過分析「藥物-成分-靶點-疾病」網絡，找到靈芝酸DM和(+)-靈芝酸甲酯A可能是靈芝治療濕疹的主要活性成分。對PPI網絡的分析發現： 腫瘤壞死因子（TNF）、白介素6（IL6）、白介素1B（IL1B）、雙特異性絲裂原活化蛋白激酶1（MAP2K1）、 基質金屬蛋白酶3（MMP3）為靈芝治療濕疹的核心靶點。KEGG通路分析結果表明：靈芝治療濕疹主要與Th17 細胞分化、腫瘤壞死因子（TNF）通路有關。結論：靈芝治療濕疹的核心成分是靈芝酸DM和(+)-靈芝酸甲酯A； 核心靶點為TNF、IL6、IL1B、MAP2K1和MMP3；核心通路為Th17細胞分化和TNF通路。本研究為發現靈芝抗濕疹的分子機制及有效成分奠定了基礎。

Objective: This study aims to explore the molecular mechanisms and bioactive compounds of ganoderma in treating atopic dermatitis (eczema) by network pharmacology analysis. Methods: The components of ganoderma and their corresponding targets were collected from the TCMSP database and Swiss Target Prediction online website, respectively. Eczema-related genes were collected from OMIM, GeneCards and TTD databases. The protein-protein interaction (PPI) network was constructed using a STRING database after obtaining the common molecules of ganoderma targets and eczema-related genes. The Cytoscape3.8.2 software and R programming language were used to analyze and visualize the networks. Results: A total of 61 active ingredients of ganoderma were collected, and 101 common genes of Ganoderma targets and eczema-related genes were identified. By analyzing the "herb-bioactive compound-target-disease" network, we found that ganoderma acid DM and (+) methyl ganolucidate A may be the main bioactive compounds of ganoderma in treating eczema. PPI network analysis shows that tumor necrosis factor (TNF)Z interleukin 6 (IL6), interleukin 1B (IL1B), mitogen-activated protein kinase Kinase 1 (MAP2K1) and matrix metalloproteinase 3 (MMP3) are the core anti-eczema targets of ganoderma. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that Th17 cell differentiation and TNF signaling pathway may be involved in the anti-eczema effects of ganoderma. Conclusion: The core components of Ganoderma in treating eczema are ganoderma acid DM and (+) methyl ganolucidate A. The core targets involved in the anti-eczema effects of ganoderma are TNF, interleukin (IL)-6, I L1B, MAP2K1, and MMP3, while the involved core pathways are Th17 cell differentiation and the TNF signaling pathway. This study lays a foundation for investigating the anti-eczema mechanisms and bioactive compounds of ganoderma.